Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood
Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood
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DOI：
10.1002/ajmg.b.32323
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发表时间：
2015-07-01
影响因子：
2.8
通讯作者：
Avramopoulos, Dimitrios
中科院分区：
文献类型：
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作者：
Hatzimanolis, Alex;Bhatnagar, Pallav;Avramopoulos, Dimitrios
神经认知能力是具有相当遗传性的复杂特征。受损的神经认知通常在精神分裂症（SZ）中观察到，而收敛的证据表明神经认知和SZ之间有共同的遗传决定因素。在这里，我们报告了一个全基因组关联研究（GWAS）的神经心理学和眼科特征，与SZ，在一般人群样本的健康年轻男性（n=1079）。在相同表型的内部样本（n=738）和具有可比神经心理学测量的年轻男性的独立队列（n=825）中进行后续基因分型。基于全基因组单核苷酸多态性（SNPs）确定遗传力估计值，并在人脑中评估对基因表达的潜在调节作用。利用认知基因组学联盟（COGENT）和精神病基因组学联盟（PGC-SZ）的荟萃分析GWAS结果，对一般认知能力和SZ风险多基因评分的相关性进行了测试。GWAS结果暗示了编码参与突触神经传递的蛋白质靶点的生物学相关遗传位点，尽管没有检测到稳健的个体复制，因此需要额外的验证。基于排列的二次分析显示，在言语工作记忆（WM）和反动作受试者内反应时变异性的GWAS顶级信号中，有过多的强相关位点（经验P
Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome-wide association study (GWAS) on neuropsychological and oculomotor traits, linked to SZ, in a general population sample of healthy young males (n=1079). Follow-up genotyping was performed in an identically phenotyped internal sample (n=738) and an independent cohort of young males with comparable neuropsychological measures (n=825). Heritability estimates were determined based on genome-wide single-nucleotide polymorphisms (SNPs) and potential regulatory effects on gene expression were assessed in human brain. Correlations with general cognitive ability and SZ risk polygenic scores were tested utilizing meta-analysis GWAS results by the Cognitive Genomics Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC-SZ). The GWAS results implicated biologically relevant genetic loci encoding protein targets involved in synaptic neurotransmission, although no robust individual replication was detected and thus additional validation is required. Secondary permutation-based analysis revealed an excess of strongly associated loci among GWAS top-ranked signals for verbal working memory (WM) and antisaccade intra-subject reaction time variability (empirical P